POS0645 LONG-TERM SAFETY AND EFFICACY OF OLOKIZUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS – RESULT OF AN OPEN-LABEL EXTENSION STUDY, CREDO4
Authors: E. Feist, E. Nasonov, M. Luggen, S. Fatenejad, S. Grishin, M. Samsonov, R. M. Fleischmann
Journal: Annals of the Rheumatic Diseases (2022)

Background Olokizumab (OKZ), an IL-6 ligand inhibitor, demonstrated significant improvements in signs and symptoms of RA vs placebo (PL) and non-inferiority to adalimumab (ADA) in doses of 64 mg every two weeks (q2w) or every 4 weeks (q4w). 1-3 Patients (pts) who completed core phase III studies, were enrolled in an open-label extension study (OLE) (ClinicalTrials.gov number, NCT03120949 ). Objectives To report long-term safety and efficacy results of OKZ in combination with MTX. Methods During the OLE study, pts continued OKZ 64 mg q2w or q4w, and those who were on PBO or ADA were randomized to OKZ 64 mg q2w or q4w. Adverse events (AE) were assessed through 82 weeks of the OLE treatment and an additional 20 weeks of safety follow-up. All AEs were analyzed using descriptive statistics. Efficacy assessments included proportions of pts who achieved ACR20/50/70 responses, SDAI ≤3.3, improvement in HAQ-DI ≥0.22, mean change in CDAI, and DAS-28-CRP using descriptive statistics. Results 2105 eligible pts were enrolled, 1709 (81.2%) pts completed the OLE treatment period and 394 (18.7%) pts discontinued treatment, mainly due to adverse events 180 (8.6%), due to subject decision 158 (7.5%) and due to lack of efficacy 9 (0.4%). Treatment emergent AE occurred in 1546 (73.5%) pts, the most common AE 809 pts (38.5%) were infections (Table 1). The most common AE leading to treatment discontinuation were infections (53 [2.5%]), investigations (43 [2.0%]) including 1% with ALT increase and blood and lymphatic system disorders (13 [0.6%]) including leuko- and lymphopenia (0.2%-0.1%). Serious AE were reported by 249 (11.8%) pts, serious infections - by 87 (4.1%) pts. Deaths occurred in 1.2% of pts, equally distributed between the two groups with the most frequent reason being infections. Efficacy of OKZ was maintained throughout the OLE (Figure 1) and pts who switched from PBO or ADA showed the same level of improvement as those who were treated with OKZ in the core studies (data not shown). Figure 1. Mean CDAI over time (modified Intent-to-treat population). Abbreviations : CDAI, clinical disease activity index. There were no apparent differences in safety and efficacy outcomes between OKZ arms, except incidence of major adverse cardiovascular events appeared slightly higher in q4w arm (Figure 1, Table 1). Anti-drug antibodies occurred infrequently and neutralizing antibodies were rare. Conclusion OKZ was safe and well-tolerated that is consistent with the results of previously reported studies of OKZ and IL-6 inhibitors. Efficacy of OKZ was maintained through Wk 82 and discontinuation rates were low. References [1]Feist E, et al. Arthritis Rheumatol. 2021; 73 (suppl 10): 3508-10; [2]Feist E, et al. Arthritis Rheumatol. 2021; 73 (suppl 10): 3510-13; All cases, n (%) OKZ 64 mg q2w (OLE), N=1061 OKZ 64 mg q4w (OLE), N=1043 Any AE 793 (74.7%) 753 (72.2%) Any serious AE 120 (11.3%) 129 (12.4%) Any AE leading to discontinuation of study drug 90 (8.5%) 87 (8.3%) Any death 13 (1.2%) 13 (1.2%) Any AE of special interest 611 (57.6%) 598 (57.3%) Infections 398 (37.5%) 389 (37.3%) Opportunistic infections 22 (2.1%) 19 (1.8%) Malignancies 6 (0.6%) 9 (0.9%) Basal cell carcinomas 1 (&lt;0.1%) 2 (0.2%) Hyperlipidemia 138 (13.0%) 120 (11.5%) Systemic injection and hypersensitivity reactions 100 (9.4%) 99 (9.5%) Anaphylactic reactions 0 0 Gastrointestinal perforation 2 (0.2%) 1 (&lt;0.1%) Neutro-, thrombocyte-, leukocyte-, pan-cytopenias 168 (15.8%) 146 (14.0%) Potential hepatotoxicity (ALT &gt;3 ULN) 63 (5.9%) 68 (6.5%) Injection site reactions 34 (3.2%) 34 (3.3%) Demyelination in peripheral or central nervous system 1 (&lt;0.1%) 0 Autoimmune disorders 41 (3.9%) 48 (4.6%) Serious infection 47 (4.4%) 40 (3.8%) Any potential adjudicated major adverse cardiac events 7 (0.7%) 15 (1.4) AE, adverse event; ALT, alanine aminotransferase; n, number of subjects; %, percentage of subjects calculated relative to the total number (N) of subjects in the population; ULN, upper limit normal [3]Nasonov E, et al. Ann Rheum Dis. 2021; 0:1–11 Acknowledgements R-Pharm funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Sofia Kuzkina, MD, (Moscow, RF) R-Pharm employee. Disclosure of Interests Eugen Feist Consultant of: Abbvie, BMS, Eli Lilly, Gilead Sciences, Galapagos, Medac, Novartis, Roche, Sanofi, Sobi, R-Pharm, Grant/research support from: BMS, Eli Lilly, Novartis, Roche, Evgeny Nasonov Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Michael Luggen Grant/research support from: Abbvie, Biogen, GSK, Lilly, R-Pharm, Sun Pharma, and UCB, Saeed Fatenejad Shareholder of: Pfizer, INC, Consultant of: ICON and PPD contract research organizations, R-Pharm, Sergey Grishin Employee of: R-Pharm, Mikhail Samsonov Employee of: R-Pharm, Roy M. Fleischmann Consultant of: AbbVie, BMS, Gilead, Galvani, GSK, Janssen, Eli Lilly, Novartis, Pfizer, R-Pharm, UCB